Carbon Ion Radiotherapy for Hepatocellular Carcinoma: Phase I/II and Phase II Clinical Trials

Purpose:To evaluate the safety and efficacy of carbon ion radiotherapy (CIRT) for hepatocellular carcinoma (HCC)Patients and Methods: Eligibility criteria for this study were as follows: biopsy-proven HCC; recurrent or residual tumor after other ineffective treatments or no indication for any other treatment; no tumor thrombosis of the portal main branch; no other viable lesion outside the planning target volume; no prior radiotherapy for target tumors; hepatic disorder of Child-Pugh grade A or B; Karnofsky performance status of 60-100; no other active cancer; and digestive tract not in contact with clinical target volume. CIRT was administered in 15 fractions for 5 weeks for 24 patients, 12 fractions for 3 weeks for 34 patients, 8 fractions for 2 weeks for 24 patients, 4 fractions for 1 week for 75 patients, or 2 fractions for 2 days for 32 patients within Phase I/II or Phase II clinical trials. Total dose ranged from 49.5 cobalt gray equivalent (GyE) in 15 fractions to 38.8 GyE in 2 fractions.Results:Between April 1995 and February 2005, 189 patients were totally enrolled. The subjects of this report were 181 patients with follow-up period of over 6 months, 13 of whom were twice treated with CIRT in this study. Therefore, the number of subjects for local control and survival analysis was 181 and 168, respectively. The survival period was calculated from the day of commencement of the first CIRT. The median age at therapy was 68 years (range, 37-84 years). All the patients had chronic liver diseases of Child-Pugh grade A in 145, B in 33, and inevaluable in 3. Ninety-six patients (53%) had intrahepatic recurrent lesions. The median tumor size was 4.0 cm in diameter (range, 1.2-12.0 cm). During a median follow-up of 58 months (range, 8-118 months), no hepatic failure resulting from the therapy and no treatment-related death occurred. Incidence of grade 3 early hepatic toxicity according to NCI-CTC was 13%, 1%, 2%, 8%, and 0% in the serum-GPT, ALB, T.BIL, prothrombin activity (PT%) and ALP, essential valuables concerning hepatic function, respectively. No grade 4 toxicity occurred with exception of 1 patient in T.BIL. No other grade 3 or worse adverse effect occurred. In 92% and 81% of the evaluable patients, the Child-Pugh score did not increase by more than 1 point in the early and late phase, respectively. Local control rate was 94%, 88%, and 88% at 1, 3, and 5 years, respectively. Overall survival rate was 93%, 54%, and 29% at 1, 3, and 5 years, respectively. The rate in the 27 patients initially treated with CIRT of 52.8GyE/4-fraction in the phase II study was 96% and 71% at 1 and 3 years, respectively, that was comparable with that in the hepatic resection in Japan. Conclusion:Carbon ion radiotherapy for hepatocellular carcinoma, especially short-course carbon ion radiotherapy of 52.8GyE/4-fraction, seems to be safe and effective, and to have a promising potential as a new, radical, and minimally invasive therapeutic option for Hepatocellular Carcinoma.第42回 Particle Therapy Co-operative Group Meetin